MCH over-expressing transgenic mice are mildly obese, and both MCH−/− and MCHR1−/− mice are characterized by reduced weight gain relative to wild type controls. MCH-induced body weight gain and hyperphagia are absent in MCHR1 null mice. Non-peptide small molecule MCHR1 antagonists attenuate food intake stimulated by MCH. The forgoing support the hypothesis to treat obesity and related diseases with compounds that are effective antagonists of MCHR1.
PCT application number WO 2003/033476A1 discloses compounds reportedly useful as antagonists of the MCH receptor. PCT application number WO 2003/033480A1 discloses compounds reportedly useful as antagonists of the MCH receptor. PCT application WO 2006/066174A1 discloses compounds useful in the treatment, prevention or amelioration of symptoms associated with obesity and related diseases.
Current treatments targeted at obesity have not proven effective for all patients and for sustainable periods of time. Examples of such treatments include various over-the-counter appetite suppressants, various dietary regimens and/or exercise. Therefore, there is a need for new and/or improved therapeutically effective agents useful for treating, preventing and/or ameliorating the effects of obesity.
Antagonists of MCHR1 would be expected to be useful to treat or prevent obesity and related diseases. There is a need to find potent antagonists of MCHR1. There is also a need to find compounds that selectively bind MCHR1 relative to MCHR2. There also exists a need to find MCHR1 antagonists having an improved safety profile over the prior art compounds. The present invention provides such potent, selective MCHR1 antagonists having an improved safety profile for the treatment of obesity and related diseases.